Multi-reflecting mass spectrometer with high throughput

Abstract

Method and embodiments are provided for tandem mass spectrometer designed for extremely large charge throughput up to 1E+10 ion/sec. In one operation mode, the initial ion flow with wide m/z range is time separated in a trap array. The array ejects ions with a narrower momentarily m/z range. Ion flow is collected and confined in a wide bore ion channel at a limited time spread. The ion flow with narrow m/z range is then analyzed in a multi-reflecting TOF at frequent and time-encoded operation of the orthogonal accelerator, thus forming multiple non overlapping spectral segments. In another mode, time separated ions are subjected to fragmentation for comprehensive, all-mass MS-MS analysis. The momentarily ion flow at MR-TOF entrance is characterized by lower spectral population which allows efficient decoding of overlapping spectra. Those modes are combined with conventional spectrometer operation to improve the dynamic range. To provide practical solution, there are proposed multiple novel components comprising trap arrays, wide bore confining channels, resistive multipole, so as long life TOF detector.

What we claim is: 
     
       1. A method of high charge throughput mass spectral analysis comprising the steps of:
 generating ions in a wide m/z range in an ion source; 
 within a first mass separator, mass separating an ion flow in time according to ionic m/z with resolution between 10 and 100; and 
 high resolution R2>50,000 mass spectral analysis in a time of-flight mass analyzer, triggering pulses of said time-of-flight mass analyzer at period being much shorter compared to ion flight time in said time-of-flight mass analyzer, such that to minimize or avoid spectral overlaps between signals produced by individual starts at injection of ions of a narrower m/z window due to temporal separation in the first mass separator. 
 
     
     
       2. A method as in  claim 1 , further comprising the step of fragmenting ions between said stages of mass separation and mass analysis, wherein triggering pulses of said time-of-flight mass analyzer are time encoded for unique time intervals between any pair of triggering pulses within a flight time period. 
     
     
       3. A method as in  claim 1 , wherein said step of crude mass separation separating comprises time separating within a multichannel ion trap or within a wide bore and spatial focusing time-of-flight mass analyzer preceded by a multichannel trap pulse converter. 
     
     
       4. A method as in  claim 1 , further comprising a step of bypassing said first mass separator for a portion of time and admitting a portion of ion flow from said ion source into said time-of-flight mass analyzer to analyze most abundant ion species without saturating space charge of said time-of-flight mass analyzer or to avoid saturation of a detector. 
     
     
       5. A method of high charge throughput mass spectral analysis comprising the following steps:
 a. For a chromatographically separated ion flow, in an ion source, generating a plurality of ions in a wide range of ion m/z and passing said ion flow with up to 1E+10 ion/sec into an radio-frequency ion guide at an intermediate gas pressure; 
 b. splitting said ion flow between multiple channels of a radiofrequency confining ion buffer; 
 c. accumulating said ion flow in said ion buffer and periodically ejecting at least a portion of the accumulated ion flow into a multichannel trap; 
 d. dampening ions in said multichannel trap in collisions with Helium gas at gas pressure between 10 and 100 mTor in multiple RF and DC trapping channels, the number N of said trapping channels being greater than 10 and the length L of individual channels are chosen such that the product L*N>1 m; 
 e. sequentially ejecting ions out of said multichannel trap progressively with ion m/z either in direct or reverse order, so that ions of different m/z will be separated in time with resolution R1 between 10 and 100; 
 f. accepting the ejected and time separated ion flow from said multichannel trap into a wide open RF ion channel and driving ions with a DC gradient for rapid transfer with time spread less than 0.1-1 ms; 
 g. spatially confining said ion flow by RF fields while maintaining the prior achieved time separation with less than 0.1-1 ms time spread; 
 h. forming a narrow ion beam with ion energy between 10 and 100 eV, beam diameter less than 3 mm and angular divergence of less than 3 degree at an entrance of an orthogonal accelerator; 
 i. forming ion packets with said orthogonal accelerator at a frequency between 10 and 100 kHz with uniform pulse period or pulse period being encoded to form unique time intervals between said pulses; due to on mass separating in step (e), said ion packets contain ions of at least 10 times narrower mass range compared to initial m/z range generated in said ion source; 
 j. analyzing ion flight time of said ion packets with momentarily narrow m/z range in multi-reflecting electrostatic fields of a multi-reflecting time-of-flight mass analyzer with ion flight time for 1000 Th ions of at least 300 us and with mass resolution above 50,000; and 
 k. recording signals past the time-of-flight mass analyzer by a detector with sufficient life time to accept over 0.0001 Coulomb at a detector entrance. 
 
     
     
       6. A method as in  claim 5 , further comprising a step of fragmenting ions between said step of mass sequentially ejecting and said step of analyzing ion flight time of said ion packets in high resolution time-of-flight mass analysis. 
     
     
       7. A method as in  claim 5 , for extending dynamic range and for analyzing major analyte species, further comprising a step of admitting and analyzing with said high resolution time-of-flight mass analyzer of at least a portion of the original ion flow of wide m/z range. 
     
     
       8. A method as in  claim 5 , wherein said step of mass separating in a trap array comprises one step of the list: (i) radially ejecting ions out of a linearly extended RF quadrupole array by quadrupolar DC field; (ii) radially ejecting resonant ions out of the linearly extended RF quadrupole array; (iii) selectively mass ejecting axial ions out of the RF quadrupole array; (iv) selectively mass transferring axial ions within an array of RF channels having radial RF confinement, an axial RF barrier, and axial DC gradient for ion propulsion, all formed by distributing DC voltage, RF amplitudes and phases between multiple annular electrodes; and (v) ejecting ions by DC field out of multiple quadrupolar traps fed by ions through an orthogonal RF channel. 
     
     
       9. A method as in  claim 5 , wherein a mass separator array is arranged either on a planar, or at least partially cylindrical or spherical surface, said mass separator array is geometrically matched with ion buffers and ion collecting channels of a matching topology. 
     
     
       10. A method as in  claim 5 , wherein said step of mass separating is arranged in Helium at gas pressure from 10 to 100 mTor for accelerating and transferring said ions past said step of crude mass separating. 
     
     
       11. A method as in  claim 5 , further comprising a step of an additional mass separating said ions between said step of sequentially ejecting ions and said step of ion orthogonally accelerating ions into said multi-reflecting time-of-flight mass analyzer, wherein said step of additional mass separating said ions comprises one step of the list: (i) sequentially mass dependent ejecting ions out of an ion trap or a trap array; (ii) mass filtering said ions in a mass spectrometer, said mass filtering being mass synchronized with a first mass dependent ejection. 
     
     
       12. A tandem mass spectrometer comprising:
 a comprehensive multi-channel trap array for sequential ion ejection according to their m/z in T1=1 to 100 ms time at resolution R1 between 10 and 100; 
 an RF ion channel with sufficiently wide entrance bore for collecting, dampening, and spatial confining of the majority of said ejected ions at 10 to 100 mTor gas pressure, said RF ion channel having an axial DC gradient for sufficiently short time spread ΔT<T1/R1 to sustain the temporal resolution of a first comprehensive mass separator; 
 a multi-reflecting time-of-flight (MR-TOF) mass analyzer; 
 an orthogonal accelerator with frequent encoded pulsed acceleration placed between said multi-channel trap array and said MR-TOF mass analyzer; 
 a clock generator for generating start pulses for said orthogonal accelerator, wherein period between said pulses is at least 10 times shorter compared to flight time of heaviest m/z ions in said MR-TOF mass analyzer, and wherein the time intervals between said pulses are either equal or encoded for unique intervals between any pair of pulses within the flight time period; and 
 a time-of-flight detector with a life time exceeding 0.0001 Coulomb of the entrance ion flow. 
 
     
     
       13. The tandem mass spectrometer as in  claim 12 , further comprising a fragmentation cell between said multi-channel trap array and said orthogonal accelerator. 
     
     
       14. The tandem mass spectrometer as in  claim 12 , wherein said multi-channel trap array comprises multiple traps of a group: (i) linearly extended RF quadrupole with quadrupolar DC field for radial ion ejection; (ii) linearly extended RF quadrupole for resonant ion radial ejection; (iii) RF quadrupole with DC axial plug for mass selective axial ion ejection; (iv) annular electrodes with distributed DC voltages, RF amplitudes and phases between electrodes to form an RF channel with radial RF confinement, an axial RF barrier, and an axial DC gradient for ion propulsion; and (v) quadrupolar linear trap fed by ions through an orthogonal RF channel for ion ejection by DC field through an RF barrier. 
     
     
       15. The tandem mass spectrometer as in  claim 12 , further comprising a mass separator array arranged either on a planar, or at least partially cylindrical or spherical surface, where said mass separator array is geometrically matched with ion buffers and ion collecting channels of a matching topology.